Method for metal-organic production of organic intermediate products by means of aryl lithium-bases

ABSTRACT

The invention relates to a method for the production of substituted aromatic compounds by producing lithium arylene and by reacting it with suitable electrophiles. The method comprises the following steps (step 1); an aryl lithium compound ( auxiliary base”) is initially produced by reacting a halogen aromatic compound with lithium metal; said compound is subsequently (step 2) reacted for deprotonation of the aromatic substrate in order to form the corresponding lithium aromatic compound which is subsequently (step 3) reacted with a corresponding electrophile to form the desired substituted aromatic compound, see page 2 of the description.

The invention relates to a process for preparing substituted aromaticcompounds by generation of lithium aryls and reaction of these withsuitable electrophiles, in which a haloaromatic is firstly (step 1)reacted with lithium metal to generate an aryllithium compound(“auxiliary base”) which is subsequently (step 2) reacted with thearomatic substrate to deprotonate the latter and form the correspondinglithioaromatic, and this is finally (step 3) reacted with an appropriateelectrophile to form the desired substituted aromatic compound (equation1).Step 1: Generation of the Base

Step 2: Deprotonation of the Substrate

Step 3: Reaction of the Aryllithium Compound with an Electrophile

(Equation 1)

The upswing in organometallic chemistry, in particular that of theelement lithium, in the preparation of compounds for the pharmaceuticaland agrochemicals industries and also for numerous further applicationshas progressed almost exponentially in the past few years if the numberof applications or the quantity of products produced in this way isplotted against a time axis. Significant reasons for this are, firstly,the evermore complex structures of the fine chemicals required for thepharmaceuticals and agrochemicals sectors and, secondly, the virtuallyunlimited synthetic potential of organolithium compounds for building upcomplex organic structures. Almost any organblithium compound can begenerated easily by means of the modern Arsenal or organometallicchemistry and be reacted with virtually any electrophiles to form therespective desired product. Most organolithium compounds are generatedusing of the following routes:

(1) the most important route is without doubt halogen-metal exchange inwhich (usually) bromoaromatics are reacted with n-butyllithium at lowtemperatures

(2) some organolithium compounds can be prepared by reactingbromoaromatics with lithium metal, as long as no interfering groupswhich react with Li metal are present in the molecule,

(3) furthermore, the deprotonation of organic compounds using lithiumalkyls (e.g. BuLi) or lithium amides (e.g. LDA or LiNSi) is veryimportant

It can be seen from this that the use of commercial alkyllithiumcompounds is required for the major part of this chemistry, with N-BuLimostly being used here. The synthesis n-BuLi and relatedlithioaliphatics is technically complicated and requires a great deal ofknow-how, as a result of which n-butyllithium, s-butyllithium,tert-butyllithium and similar molecules are, from an industrialviewpoint, offered at very high prices. This is the most important butfar from the only disadvantage of this otherwise very advantageous andwidely usable reagent.

Owing to the extreme sensitivity and, in concentrated solutions,pyrophoric nature of such lithioaliphatics, very costly logisticssystems for transport, introduction into the metering reservoir andmetering have to be provided for the large amounts (annular productionquantities of from 5 to 500 metric tons) wanted in large-scaleindustrial production.

Furthermore, the reactions of n-, s- and tert-butyllithium form eitherbutanes (deprotonations), butyl halides (halogen-metal exchange, oneequivalent of BuLi) or butene and butane (halogen-metal exchange) whichare gaseous at room temperature and are given off in the necessaryhydrolytic work-ups of the reaction mixture. As a result, complicatedoffgas purifications or appropriate incineration facilities are alsonecessary in order to meet strict pollution laws. As a way of avoidingthis, specialist companies are offering alternatives such asn-hexyllithium which do not result in formation of butanes, but aresignificantly more expensive than butyllithium.

A further disadvantage is that complex solvent mixtures are obtainedafter the work-up. Adding to the high reactivity of alkyllithiumcompounds toward ethers, which are virtually always used as solvents forthe subsequent reactions, alkyllithium compounds can usually not bemarketed in these solvents. Although the producers offer a broad rangeof alkyllithium compounds in various concentrations in varioushydrocarbons, halogen-metal exchange reactions, for example, do notproceed in pure hydrocarbons, so that one is forced to work in mixturesof ethers and hydrocarbons. After hydrolysis, this results inwater-containing mixtures of ethers and hydrocarbons whose separation iscomplicated and can in many cases not be carried out economically atall. However, recycling of the solvents used is an indispensableprerequisite for large-scale industrial production.

For the reasons mentioned, it would therefore be very desirable to havea process in which the use of such commercially available organolithiumcompounds can be avoided. An in-situ variant using alkyl halides/lithiummetal have been described by us in the German patent application 101 50615.4-44, which is not a prior publication. For various reasonsassociated with the easier isolation of the protonated auxiliary base,with a frequently smaller critical by-product spectrum and with oftencheaper aryl halides, the use of aryl halides/lithium metal as“auxiliary bases” would in many cases be even more advantageous.

The present invention achieves these objects and provides a process forpreparing aryllithium compounds of the formulae (V) and (VI) andreacting them with suitable electrophiles to give compounds of theformulae (VII) and (VIII), in which aryl halides of the formula (I) arefirstly (“two-stage variant”) or if appropriate in the presence of theelectrophilic compound (substrate) (“in-situ variant”) with lithiummetal to generate a lithium compound (II), this is used fordeprotonating the aromatic substrate (III) or (IV), and is finelyconverted by addition of the electrophilic component into the targetcompound of the formula (VII) or (VIII) (equation 1),Step 1: Generation of the Base

Step 2: Deprotonation of the Substrate

Step 3: Reaction of the Aryllithium Compound with an Electrophile

(Equation 1)where Ar is phenyl, alkyl-substituted phenyl, fluorine- orchlorine-substituted phenyl, naphthyl-, alkyl-substituted naphthyl or isbiphenyl,Hal=fluorine, chlorine, bromine or iodine,the radicals X₁₋₄ are, independently of one another, either carbon,X_(i)R_(i) (i=1-4) can symbolize nitrogen, or two radicals X_(i)R_(i)which are adjacent or connected via a formal double bond can together beO (furans), S (thiophenes), NH or NR_(i) (pyrroles),Z is, in the case of benzoidal aromatics, a group which activates theortho position, for example CF₃, OCF₃, Cl, F, Oalkyl, Oaryl, Salkyl,Saryl, CH₂OH, CH₂OR, CH(OR)₂, CONR₂, NHR, NR₂, or in the case ofheterocycles has the same meaning as R₁₋₄,the radicals R₁₋₄ are substituents selected from the group consisting ofhydrogen, methyl, primary, secondary or tertiary, cyclic or acyclicalkyl radicals having from 2 to 12 carbon atoms, substituted cyclic oracyclic alkyl groups, alkoxy, dialkylamino, alkylamino, arylamino,diarylamino, phenyl, substituted phenyl, alkylthio, diarylphosphino,dialkylphosphino, dialkylaminocarbonyl or diarylaminocarbonyl,monoalkylaminocarbonyl or monoarylaminocarbonyl, CO₂alkyl, CO₂ ⁻,1-hydroxyalkyl, 1-alkoxyalkyl, fluorine or chlorine, CN or heteroaryl,where two adjacent radicals R₁₋₄ can together correspond to a fused-onaromatic or aliphatic ring,and “Electrophile” is any electrophilic component which can be reactedwith aryllithium compounds.

Preferred compounds of the formula (III) or (IV) which can be reacted bythe process of the invention are, for example, benzenes, furans,thiophenes, pyridines, pyridazines, pyrimidines, pyrazines,N-substituted pyrroles, benzofurans, indoles or naphthalenes, to nameonly a few.

The organolithium compounds prepared in this way can be reacted with anyelectrophilic compound by methods of the prior art. C,C couplings, forexample, can be carried out by reaction with carbon electrophiles,boronic acids can be prepared by reaction with boron compounds, and anefficient route to organosilanes is provided by reaction withhalosilanes or alkoxysilanes.

As haloaromatics, it is possible to use all available or procurablefluoroaromatics, chloroaromatics, bromoaromatics or iodoaromatics, sincelithium metal reacts readily with all haloaromatics in ether solvents,giving quantitative yields in virtually all cases. Preference is givento using chloroaromatics or bromoaromatics, since iodo compounds areoften expensive and fluorine compounds lead to the formation of LiFwhich can, as HF, lead to material problems in the later aqueouswork-ups. In specific cases, however, such halides may be able to beused advantageously. Particular preference is naturally given tocommercially available aryl chlorides such as chlorobenzene, butespecially the isomeric chlorotoluenes. It is even possible to useindustrial isomer mixtures which in many cases are even cheaper.

The reaction is carried out in a suitable organic solvent, preferably anether solvent such as tetrahydrofuran (THF), dioxane, diethyl ether,di-n-butyl ether, a glyme or diisopropyl ether. Preference is given tousing THF.

Adding to the high reactivity of aryllithium compounds, in particularalso toward the ethers used as solvents, the preferred reactiontemperatures are in the range from −100 to +35° C., particularlypreferably from −70 to +25° C.

Apart from the abovementioned advantages of the procedure according tothe invention (costs, logistics, safety, gaseous by-products), a furtheradvantage is that it is possible to work at quite high concentrations oforganolithium compounds. This results, in particular, from the fact thatthe use of, for example, butyl lithium in commercial concentrationsintroduces from five to six times the volume of solvent. Preference isgiven to concentrations of the aliphatic or aromatic intermediates ofthe formula (II) or (IV) of from 5 to 30% by weight, in particular from12 to 25% by weight.

In addition, high selectivities are frequently also observed, which isdue to the fact that the reaction can be carried out in pure ethersinstead of ether/hydrocarbon mixtures.

In the preferred embodiment, haloaromatic and aromatic substrates areadded simultaneously or as a mixture to the lithium metal in the ether.In this one-pot variant, the lithioaromatic is formed first and thenimmediately deprotonates the actual substrate. In a second preferredembodiment which can be employed especially when the aromatic canundergo secondary reactions with metallic lithium, it is possiblefirstly to generate the aryllithium compound in an ether by reaction ofthe haloaromatic and lithium and only then add the aromatic substratebefore the targeted molecule is finally produced by reaction with anelectrophile.

In addition, it has surprisingly been found that in the preferredembodiment as a one-pot reaction, significantly higher yields than whenArLi is generated first and the aromatic substrate is only addedsubsequently are observed in very many cases.

In the present process, the lithium can be used as dispersion, powder,turnings, sand, granules, pieces, bars or in another form, with the sizeof the lithium particles not being relevant to quality but merelyinfluencing the reaction times. Preference is therefore given torelatively small particle sizes, for example granules, powders ordispersions. The amount of lithium added per mole of halogen to bereacted is from 1.95 to 2.5 mol, preferably from 1.98 to 2.15 mol.

In all cases, significant increases in the reaction rates and frequentlyalso increases in yield can be observed when organic redox systems, forexample biphenyl, 4,4′-di-tert-butylbiphenyl or anthracene, are added.It is usually sufficient to add these compounds in amounts of <0.5 mol%, usually even <0.02 mol %.

Aromatics which can be used for the deprotonation are all compoundswhich are sufficiently acidic to be able to be deprotonated under theconditions according to the invention. These are firstly all thosearomatics which have strongly “ortho-directing” substituents Z, i.e., inparticular, aromatics which bear alkoxy, CF₃, F, Cl, substituted amino,CN, heteroaryl, aminoalkyl, hydroxyalkyl or similar radicals. The modeof action of such radicals is based on the substituents making itpossible for the lithium ions to coordinate to the aliphatic base, as aresult of which the counterion Ar can then be deprotonated very easilyin the ortho position.

Furthermore, all heterocycles which are strongly acidic due to thecombination of a plurality of effects, for example furan, may bementioned in this context. Here, the protons are sufficiently acidic tomake deprotonation possible as a result of, inter alia, the inductiveeffect of the oxygen and also the sp hybridization and the angularstress on the a carbon. The same applies to other heterocycles.

The lithioaromatics generated according to the invention can be reactedwith electrophilic compounds by methods with which those skilled in theart are familiar, with carbon, boron and silicon electrophiles being ofparticular interest with a view to the intermediates required for thepharmaceutical and agrochemicals industries.

The carbon electrophiles come, in particular, from one of the followingcategories (the products as shown in brackets in each case):

oxirane, substituted oxiranes (ArCH₂CH₂OH, ArCR₂CR₂OH) where R═R¹(identical or different)

azomethines (ArCR₂—NR′H)

aryl or alkyl cyanates (benzonitriles)

nitroenolates (oximes)

immonium salts (aromatic amines)

haloaromatics, aryl triflates, other aryl sulfonates (biaryls)

carbon dioxide (ArCOOH)

carbon monoxide (Ar—CO—CO—Ar)

aldehydes, ketones (ArCHR¹—OH, ArCR₂—OH)

α,β-unsaturated aldehydes/ketones (ArCH(OH)-vinyl, CR¹(OH-vinyl ketenes(ARC(═O)CH₃ in the case of ketene, (ArC(═O)—R¹ in the case ofsubstituted ketenes)

alkali metal and alkaline earth-metal salts of carboxylic acids (ArCHOin the case of formates, ArCOCH₃ in the case of acetates, ArR¹CO in thecase of R¹COOMet)

aliphatic nitriles (ArCOCH₃ in the case of acetonitrile, ArR¹ CO in thecase of R¹CN)

aromatic nitriles (ArCOAr′)

amides (ArCHO in the case of HCONR₂, ArC(═O)R in the case of RCONR′₂)

esters (Ar₂C(OH)R¹) or

alkylating agents such as alkyl halides or alkyl sulfonates (Ar-alkyl).

Boron electrophiles used are compounds of the formula BW₃, where theradicals W are identical or different and are each C₁-C₆-alkoxy,fluorine, chlorine, bromine, iodine, N(C₁-C₆-alkyl)₂ or S(C₁-C₅-alkyl),with preference being given to trialkoxyboranes, BF₃ OR₂, BF₃ THF, BCl₃or BBr₃, particularly preferably trialkoxyboranes.

Silicon electrophiles used are compounds of the formula SiW₄, where theradicals W are identical or different and each C₁-C₆-alkoxy, fluorine,chlorine, bromine, iodine, N(C₁-C₆-alkyl)₂ or S(C₁-C₅-alkyl), withpreference being given to tetralkoxysilanes, tetrachlorosilanes orsubstituted alkylhalosilanes or arylhalosilanes or substitutedalkylalkoxysilanes or arylalkoxysilanes.

The work-ups are generally aqueous, with either water or aqueous mineralacids being added or the reaction mixture being introduced into water oraqueous mineral acids. To achieve the best yields, the pH of the productto be isolated is in each case such, i.e. usually a slightly acidic pH,or in the case of heterocycles also a slightly alkaline pH. The reactionproducts are obtained, for example, by extraction and evaporation of theorganic phases, or, as an alternative, the organic solvents can also bedistilled off from the hydrolysis mixture and the product which thenprecipitates can be isolated by filtration.

The purities of the products from the process of the invention aregenerally high, but a further purification step, for example byrecrystallization with addition of small amounts of activated carbon,may be necessary for special applications (pharmaceutical precursors).The yields of the reaction products are from 70 to 99%; typical yieldsare, in particular, from 85 to 95%.

The process of the invention provides a very economical method ofbringing about the transformation of an aromatic hydrocarbon into anyradicals in a very economical way.

The process of the invention is illustrated by the following examples,without the invention being restricted thereto.

EXAMPLE 1 Preparation of 5-formylfuran-2-boronic acid from furfuraldiethyl acetal and p-chlorotoluene

A mixture of 22.3 g of p-chlorotoluene (0.176 mol), 27.2 g of furfuraldiethyl acetal (0.16 mol) is added dropwise to a suspension of 2.35 g oflithium granules (0.34 mol) and 0.02 g of biphenyl in 300 g of THF at−65° C. over a period of one hour, with 1.5 hours being selected asmetering time. When the conversion of the p-chlorotoluene as determinedby GC is >97% (total time of 9 h), 18.3 g of trimethyl borate (0.176mol) are added dropwise at the same temperature over a period of 30minutes. After stirring for another 30 minutes at −65° C., the reactionmixture is added to 120 g of water, 37% strength HCl is added to adjustthe pH to 6.3 and THF and toluene are distilled off at up to 35° C.under reduced pressure. The pH is then adjusted to 1.5, the mixture isstirred until the product has precipitated completely and the product isfiltered off. After washing with a little cold water and a little coldacetone, drying gives 18.2 g of 5-formyl-2-furanboronic acid (0.130 mol,81.5%) in the form of a fine, beige powder; HPLC purity: >99.8% a/a.

EXAMPLE 2 Preparation of 2,6-dimethoxyphenylboronic acid from resorcinoldimethyl ether and chlorotoluene (isomer mixture)

A mixture of 22.3 g of technical-grade chlorotoluene (isomer mixture,0.176 mol) and 22.1 g of resorcinol dimethyl ether (0.16 mol) is addedto a suspension of 2.35 g of lithium-granules (0.345 mol) and 0.02 g ofbiphenyl in 220 g of THF at 0° C. over a period of 2 hours. When theconversion of the chlorotoluene as determined by GC is >99% (total timeof 6 h), the reaction mixture is cooled to −50° C. 16.6 g of trimethylborate (0.16 mol) are subsequently added dropwise over a period of 30minutes. After stirring for another 30 minutes at −50° C., the reactionmixture is added to 120 g of water, 37% strength HCl is added to adjustthe pH to 6.3 and THF and toluene are distilled off at 35° C. underreduced pressure. 25 ml of methylcyclohexane are added to the productsuspension, the colorless product is filtered off with suction andwashed once with 25 ml of cold methylcyclohexane and once with 25 ml ofcold water. Drying gives 27.5 g of 2,6-dimethoxyphenylboronic acid(0.151 mol, 94%, melting point: 107° C.) in the form of colorlesscrystals; HPLC purity: >99% a/a.

EXAMPLE 3 Preparation of 2-trifluoromethyl-6-chlorobenzoic acid

22.3 g of p-chlorotoluene (0.176 mol) dissolved in 100 ml of THF areadded dropwise to a suspension of 2.35 g of lithium granules (0.34 mol)in 150 g of THF at −30° C. over a period of 1 hour. When the conversionas determined by GC has reached at least 99% (total time of 5 h), themixture is cooled to −60° C. and the metered addition of3-chlorobenzotrifluoride (31.0 g, 0.172 mol) is subsequently commenced(30 min). After stirring for another 1 hour, the introduction ofanhydrous carbon dioxide is commenced. After CO₂ absorption has ceased,the mixture is stirred at −60° C. for another 30 minutes. The reactionmixture is subsequently added to 100 g of water, 37% strength HCl isadded to adjust the pH to 3.4 and the solvents are distilled off at upto 55° C. under reduced pressure. The colorless product is filtered offwith suction and dried to give 2-trifluoromethyl-6-chlorobenzoic acid(yield: 69%) in the form of colorless crystals; HPLC purity: >99% a/a.Further 2-trifluoromethyl-6-chlorobenzoic acid can be obtained byextraction of the mother liquor with dichloromethane, drying over sodiumsulfate and evaporation; total yield: 89%.

EXAMPLE 4 Preparation of 2-trifluoromethyl-6-chlorobenzaldehyde

22.3 g of p-chlorotoluene (0.176 mol) dissolved in 100 ml of THF areadded dropwise to a suspension of 2.35 g of lithium granules (0.34 mol)in 150 g of THF at −30° C. over a period of 1 hour. When the conversionas determined by GC has reached at least 99% (total time of 5 h), themixture is cooled to −70° C. and the metered addition of3-chlorobenzotrifluoride (31.0 g, 0.172 mol) is subsequently commenced(30 min). After stirring for another 1 hour, the metered addition ofmethyl formate is commenced (0.2 mol, 12.0 g). After stirring foranother 30 minutes, the reaction mixture is subsequently added to 100 gof water, 37% strength HCl is added to adjust the pH to 6.5 and thesolvents are distilled off at up to 45° C. under reduced pressure. Theresidue is extracted twice with dichloromethane, the solution is driedover sodium sulfate and evaporated to dryness to leave2-trifluoromethyl-6-chlorobenzaldehyde as a slightly yellowish oil; HPLCpurity: >97%, yield 94%.

EXAMPLE 5 Preparation of 2,6-difluoroacetophenone from1,3-difluorobenzene and acetic anhydride

A solution of phenyllithium in THF is firstly produced by reacting 65.2g of chlorobenzene with 7.0 g of lithium granules in 400 g of THF at−25° C. When a conversion of >98% (GC a/a) has been reached, the mixtureis cooled to −65° C. and 1,3-difluorobenzene (55 g) is then added over aperiod of 30 minutes. After stirring for another 30 minutes, theresulting solution of 2,6-difluoro-1-lithiobenzene is added dropwise toa solution of 88 g of acetic anhydride in 250 g of THF which has beencooled to −5° C. After the usual aqueous work-up,2,6-difluoroacetophenone is obtained in a yield of 88%.

EXAMPLE 6 Preparation of 2-furylboronic acid from furan and triisopropylborate (“in-situ variant”)

p-Chlorotoluene (0.25 mol) and furan (0.24 mol) are simultaneously addeddropwise from two dropping funnels to a suspension of 0.52 mol oflithium granules in 300 g of THF at −15° C. over a period of 30 minutes.After a conversion of the chlorotoluene of >97% has been reached (7 h),the mixture is cooled to −60° C. and trimethyl borate (0.275 mol) issubsequently added dropwise as quickly as possible (temperature must notrise above −55° C., since otherwise too much of the corresponding boricacid is formed). The mixture is finally stirred for another 15 minutesand thawed to room temperature. After addition to 450 g of water,adjustment of the pH to 6.5 by means of dilute hydrochloric acid andvacuum distillation of the organic solvents (THF, toluene) under verymild conditions, the mixture is cooled to 5° C. Filtration of theresulting suspension, washing with ice water and cooled THF/water 80:20and drying at max. 35° C./50 mbar gives 2-furanboronic acid in a yieldof 86%.

1. A process for preparing compounds of the formulae (VII) and (VIII)via aryllithium compounds of the formulae (V) and (VI) and reaction ofthese with suitable electrophiles, aryl halides of the formula (I) arereacted with lithium metal to generate a lithium compound (II), this isused for deprotonating the aromatic substrate (III) or (IV), and isfinally converted by addition of the electrophilic component into thetarget compound of the formula (VII) or (VIII) (equation 1), and thesteps 1 to 3 are carried out as a one-pot reaction, Step 1: Generationof the Base

Step 2: Deprotonation of the Substrate

Step 3: Reaction of the Aryllithium Compound with an Electrophile

(Equation 1) where Ar is phenyl, alkyl-substituted phenyl, fluorine- orchlorine-substituted phenyl, naphthyl-, alkyl-substituted naphthyl or isbiphenyl, Hal is a halogen selected from the group consisting offluorine, chlorine, bromine, iodine, and mixtures thereof, the radicalsX₁₋₄ are, independently of one another, either carbon, X_(i)R_(i)(i=1-4) can symbolize nitrogen, or two radicals X_(i)R_(i) which areadjacent or connected via a formal double bond can together be O(furans), S (thiophenes), NH or NR_(i) (pyrroles), Z is, in the case ofbenzoidal aromatics, a group which activates the ortho position, forexample CF₃, OCF₃, Cl, F, Oalkyl, Oaryl, Salkyl, Saryl, CH₂OH, CH₂OR,CH(OR)₂, CONR₂, NHR, NR₂, or in the case of heterocycles has the samemeaning as R₁₋₄, the radicals R₁₄ are substituents selected from thegroup consisting of hydrogen, methyl, primary, secondary or tertiary,cyclic or acyclic alkyl radicals having from 2 to 12 carbon atoms,substituted cyclic or acyclic alkyl groups, alkoxy, dialkylamino,alkylamino, arylamino, diarylamino, phenyl, substituted phenyl,alkylthio, diarylphosphino, dialkylphosphino, dialkylaminocarbonyl ordiarylaminocarbonyl, monoalkylaminocarbonyl or monoarylaminocarbonyl,CO₂alkyl, CO₂ ⁻, 1-hydroxyalkyl, 1-alkoxyalkyl, fluorine or chlorine, CNor heteroaryl, where two adjacent radicals R₁₋₄ can together correspondto a fused-on aromatic or aliphatic ring, and wherein the electrophileis any electrophilic component which can be reacted with aryllithiumcompounds.
 2. The process as claimed in claim 1, wherein the compoundsof the formula (III) or (IV) are selected from the group consisting ofbenzenes, furans, thiophenes, pyridines, pyridazines, pyrimidines,pyrazines, N-substituted pyrroles, benzofurans, indoles, naphthalenes,and mixtures thereof.
 3. The process as claimed in claim 1,characterized in that the electrophile is a compound selected from thegroup consisting of oxirane, substituted oxirane, azomethine, aryl oralkyl cyanate, nitroenolate, immonium salts, haloaromatics, aryltriflates, other aryl sulfonates, carbon dioxide, carbon monoxide,aldehydes, ketones, α,β-unsaturated aldehydes or ketones, ketenes,alkali metal or alkaline earth metal salts of carboxylic acids,aliphatic nitriles, aromatic nitriles, amides, esters and alkylatingagents and boron electrophiles of the formula BW₃, where the radicals Ware identical or different and are each C₁-C₆-alkoxy, fluorine,chlorine, bromine, iodine, N(C₁-C₆-alkyl)₂ or S(C₁-C₅-alkyl), andsilicon electrophiles of the formula SiW₄, where the radicals W areidentical or different and are each C₁-C₆-alkoxy, fluorine, chlorine,bromine, iodine, N(C₁-C₆-alkyl)₂ or S(C₁-C₅-alkyl), and mixturesthereof.
 4. The process of claim 1, characterized in that the reactionis carried out in an organic ether solvent.
 5. The process of claim 1,wherein said process is carried out at a reaction temperature in a rangefrom −100 to +35° C.
 6. The process of claim 1, wherein the aromaticintermediates of the formula (II) or (IV) are present in a concentrationin a range from 5 to 30% by weight.
 7. The process of claim 1, whereinthe lithium metal is added in an amount per mole of halogen reactedranging from 1.95 to 2.5 mol.
 8. The process of claim 1, furthercomprising adding organic redox systems to the one pot reaction.
 9. Theprocess of claim 8, wherein an amount of said organic redox system addedis less than 0.5 mol-%.